Transient Bacteremia Promotes Catheter-Related Central Venous Thrombosis through Neutrophil Extracellular Traps

Abstract

Formation of intravenous catheter-related thrombosis leads to central venous stenosis in patients requiring renal replacement therapy or chemotherapy infusion, yet the triggering or mechanisms remain unclear, especially in patients without symptoms of infection. In this study, we found that neutrophil extracellular traps (NETs) could be detected in the fibrin sheaths from dialysis patients without clinical manifestations of infection. Confocal microscopy revealed bacteria imbedded in NETs in the fibrin sheaths. Thirty-nine of 50 (78%) fibrin sheath specimens contained bacteria detectable by 16S ribosomal RNA genome typing with a predominance of Staphylococcus aureus (69%). In rat models, transient bacteremia of S. aureus induced NETs in enlarged fibrin sheaths, and treatment with DNase I alone significantly reduced both NET and fibrin sheath formation surrounding the catheter. Therefore, transient bacteremia could be a silent trigger that induces NET-related immunothrombosis enhancing catheter-related central venous stenosis.

Are NETs a Novel, Exciting, Thrombosis Risk Marker?

“…Targeting NETosis or degrading existing NETs (or associated mechanistic pathways) have been extensively investigated in many disease models associated with NETs and thrombosis (27)(28)(29)(30). NETosis starts from the activation of NADPH oxidase (NOX) complex via protein kinase C (PKC)-Raf/MERK/ERK by external stimuli, followed by activation of MPO, NE and PAD4.…”

“…Targeting NETosis or degrading existing NETs (or associated mechanistic pathways) has been extensively investigated in many disease models associated with NETs and thrombosis. [27][28][29][30] NETosis starts from the activation of NADPH oxidase (NOX) complex via protein kinase C (PKC)-Raf/MERK/ERK by external stimuli, followed by activation of MPO, NE, and PAD4. PAD4 is an enzyme that catalyzes citrullination of histones and promotes chromatin de-condensation with reactive oxygen species (ROS) to induce gradual separation and loss of the nuclear membrane.…”

Neutrophil Extracellular Traps in the Infarct-Related Coronary Artery—A Marker or Mediator of Adverse Outcome?

“…Yet, excessive NET formation or reduced NET breakdown by deoxyribonucleases (DNase) may be harmful and enhance atherothrombosis mechanistically and clinically, in a range of scenarios. 4 5 6 7…”